PROJECT SUMMARY - NEUROPATHOLOGY CORE (CORE D) The mission of the Neuropathology Core at the Wisconsin Alzheimer's Disease Research Center (ADRC) is to: provide detailed characterization of brains from patients with Alzheimer's disease (AD) and other dementias; facilitate scientific and intellectual interactions between the various ADRC cores; and serve as a local and national repository for AD specimens. The Core will continue to facilitate clinical-pathologic and translational research on normal aging, mild cognitive impairment (MCI), AD, and other dementias by providing to Wisconsin ADRC and outside investigators a comprehensive resource of biospecimens, biomarker data, clinical data, and state-of-the-art diagnoses for MCI and AD, vascular, Lewy body, TDP-43, and mixed pathologies, from subjects in the Clinical Core and Wisconsin Registry for Alzheimer's Prevention (WRAP). The Neuropathology Core will generate and assemble critical diagnostic information by combining clinical data (Core B), innovative neuroimaging and biomarker assays (Core G) collected during life with brain autopsy, and morphologic, immunohistochemical, genetic, cell and molecular post-mortem analyses. The Neuropathology Core will also provide access to cutting edge tools (including genomics and proteomics) to enhance AD research on banked, frozen tissue. Additionally, the Core has taken a leadership role in setting up an induced pluripotent stem cells (iPSC) bank, with the aim of providing well-characterized stem cell lines from AD and control patients to investigators throughout the country. The Core will accomplish these goals by 1) collecting and archiving post- mortem frozen and fixed tissue blocks from multiple brain regions on deceased individuals, and ante-mortem CSF, blood, and DNA who are enrolled in the Wisconsin ADRC as well as normal elderly controls; 2) providing state-of-the-art postmortem diagnoses on Clinical Core subjects, collect National Alzheimer's Coordinating Center (NACC) neuropathology data and make the results available to the family, relevant clinicians, qualified researchers, and NACC; 3) distributing ante-mortem and post-mortem biospecimens (brain, CSF, blood products, and DNA) and neuropathologic, genetic, biomarker, and other data to suit the requirements of qualified research projects, both within UW-Madison and for national and international multi-center collaborations; 4) performing genetic and biomarker analyses in support of ADRC and outside investigators; and 5) providing well- characterized iPSC lines to local and national researchers. A flow of services is therefore envisaged whereby Wisconsin ADRC investigators and collaborators are able to obtain unambiguous post-mortem diagnosis, neuropathological data, and tissues from the Neuropathology Core together with comprehensive biomarker data (Biomarker Services) and neuroimaging data (Core G). Finally, the Core will also support advanced molecular and cellular analyses can be performed on tissues by the Biomarker and Cellular and Molecular Neuroscience Services.